POOLS OF LIPIDATED HTL-CTL CONSTRUCTS PRIME FOR MULTIPLE HBV AND HCV CTL EPITOPE RESPONSES

Various peptide-based approaches to simultaneous induction of multiple cytotoxic T lymphocyte (CTL) responses were evaluated as part of ongo ing efforts to develop immunotherapeutic vaccines for use in humans. T o this end, HLA (human histocompatibility leukocyte antigen)-A2-restri cted epitopes from several specific viral proteins were tested in an H LA-A2 transgenic mouse model system, which mimics human CTL responses to these viral proteins. Multiple CTL responses were Elicited by immun ization with either peptides emulsified in incomplete Freund's adjuvan t (IFA), or lipidated peptides administered in phosphate buffered sali ne (PBS). In the case of lipidated peptides, induction of CTL response s was crucially dependent on the presence of helper T lymphocyte (HTL) epitopes, and most efficient in the case of lipidated covalently link ed HTL-CTL epitope constructs. CTL could also be induced by immunizati on with lipidated HTL epitopes simply mixed with CTL epitopes and form ulated in PBS. However this approach was highly dependent on the parti cular lipidated HTL/CTL combination utilized and was marginally effect ive for simultaneous priming of multiple CTL responses. By contrast, a ll HTL/CTL combinations were potent immunogens when delivered as lipid ated, covalently linked molecules. This was the most effective of the approaches analysed in terms of multi-epitope priming, as demonstrated by the induction of simultaneous CTL responses to a pool of five diff erent epitopes. (C) 1998 Elsevier Science Ltd. All rights reserved.